MBE Advance Access published online on November 13, 2007
Molecular Biology and Evolution, doi:10.1093/molbev/msm196
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Research Article |
Patterns of Mutation and Selection at Synonymous Sites in Drosophila
1 Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853
2 Department of Human Genetics, University of Chicago, 920 E. 58th Street, Chicago, IL 60637
3 Institute of Biology and Centre for Bioinformatics, University of Copenhagen, Universitetsparken 15, 2100 Kbh Ø, Denmark
* To whom correspondence should be addressed (Department of Molecular Biology and Genetics, 233 Biotechnology Building, Cornell University, Ithaca, NY 14853; nds25{at}cornell.edu)
Received for publication May 22, 2007. Revision received August 13, 2007. Accepted for publication September 7, 2007.
That natural selection affects molecular evolution at synonymous sites in protein coding sequences is well established, and is thought to predominantly reflect selection for translational efficiency/accuracy mediated through codon bias. However, a recently developed maximum-likelihood framework, when applied to eighteen coding sequences in three species of Drosophila, confirmed an earlier report that the Notch gene in D. melanogaster was evolving under selection in favor of those codons defined as unpreferred in this species. This finding opened the possibility that synonymous sites may be subject to a variety of selective pressures beyond weak selection for increased frequencies of the codons currently defined as "preferred" in D. melanogaster. To further explore patterns of synonymous site evolution in Drosophila in a lineage-specific manner, we expanded the application of the maximum-likelihood framework to 8452 protein coding sequences with well-defined orthology in D. melanogaster, D. sechellia and D. yakuba. Our analyses reveal intragenomic and interspecific variation in mutational patterns, as well as in patterns and intensity of selection on synonymous sites. In D. melanogaster, our results provide little statistical evidence for recent selection on synonymous sites, and Notch remains an outlier. In contrast, in D. sechellia our findings provide evidence in support of selection predominantly in favor of preferred codons. However, there is a small subset of genes in this species that appear to be evolving under selection in favor of unpreferred codons, which indicates that selection on synonymous sites is not limited to the preferential fixation of mutations that enhance the speed or accuracy of translation in this species.
Key Words: Synonymous site • codon bias • mutational patterns
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